Many human solid tumors reside in environments with an extracellular pH (pHe) that is both sub-physiologic and lower than surrounding healthy tissue. Recent studies have shown that this low pH microenvironment can stimulate in vitro invasion and in vivo metastases. This has led to a great deal of interest in the development of non-invasive imaging strategies for measuring pH in vivo. The overall goal of this proposal is to develop a pH- responsive MR contrast agent that specifically accumulates at sites of low pHe. We hypothesize that this imaging technology will allow for the sensitive detection of 'hostile'microenvironments and will provide an important advance in the specific identification of malignant lesions. The specific aims for this proposal are (1) to synthesize pH-responsive superparamagnetic iron oxide (SPIO) nanoparticles with various physical and magnetic properties;(2) to characterize the pH-dependent uptake of pH-responsive SPIO in breast cancer cells;and (3) to quantify the size-dependent retention of pH-responsive nanoparticles in tumor xenografts. PUBLIC HEALTH RELEVANCE: We propose to develop a pH-responsive magnetic resonance contrast agent that specifically accumulates at sites of low extracellular pH. We hypothesize that this imaging technology will allow for the sensitive detection of 'hostile'tumor microenvironments and will provide an important advance in the specific identification of malignant lesions.